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Curcumin, a polyphenolic antioxidant derived from a dietary spice, exhibits anticancer activity in rodents and in humans. Its efficacy appears to be related to induction of glutathione S-transferase enzymes, inhibition of prostaglandin E2 (PGE2) production, or suppression of oxidative DNA adduct (M1G) formation. We designed a dose-escalation study to explore the pharmacology of curcumin in humans. Fifteen patients with advanced colorectal cancer refractory to standard chemotherapies consumed capsules compatible with curcumin doses between 0.45 and 3.6 g daily for up to 4 months. Levels of curcumin and its metabolites in plasma, urine, and feces were analyzed by high-pressure liquid chromatography and mass spectrometry. Three biomarkers of the potential activity of curcumin were translated from preclinical models and measured in patient blood leukocytes: glutathione S-transferase activity, levels of M1G, and PGE2 production induced ex vivo. Dose-limiting toxicity was not observed. Curcumin and its glucuronide and sulfate metabolites were detected in plasma in the 10 nmol/L range and in urine. A daily dose of 3.6 g curcumin engendered 62% and 57% decreases in inducible PGE2 production in blood samples taken 1 hour after dose on days 1 and 29, respectively, of treatment compared with levels observed immediately predose (P < 0.05). A daily oral dose of 3.6 g of curcumin is advocated for Phase II evaluation in the prevention or treatment of cancers outside the gastrointestinal tract. PGE2 production in blood and target tissue may indicate biological activity. Levels of curcumin and its metabolites in the urine can be used to assess general compliance.
The absence of sensitive markers of efficacy and compliance has frequently confounded the optimization of clinical trials of novel cancer chemopreventive agents, particularly in the case of mechanistically multitargeted diet-derived agents, such as flavonoids and other polyphenols. Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione; diferuloylmethane], a major constituent of the yellow spice turmeric derived from the rhizomes of Curcuma spp., is one such polyphenol. Curcumin has been shown to prevent cancer in the colon, skin, stomach, duodenum, soft palate, and breasts of rodents after oral administration (1, 2, 3). In clinical pilot studies in Taiwan and India, curcumin has been associated with regression of premalignant lesions of the bladder, soft palate, stomach, cervix, and skin, and with treatment responses in established malignancy (4, 5). Mechanisms by which curcumin prevents cancer are thought to involve up-regulation of carcinogen-detoxifying enzymes such as glutathione S-transferases (GST; refs. 6, 7), antioxidation (8, 9), and suppression of expression of the isoenzyme cyclooxygenase-2 (COX-2; refs. 10, 11).
The pharmacokinetic properties of curcumin in humans remain relatively unexplored. In rodents, curcumin undergoes avid metabolism by conjugation and reduction, and its disposition after oral dosing is characterized by poor systemic bioavailability (9, 12). In a pilot study of a standardized oral Curcuma extract, doses up to 180 mg of curcumin per day were administered to patients with advanced colorectal cancer for up to 4 months without overt toxicity or detectable systemic bioavailability (13). A subsequent study has suggested that doses up to 8 g could be administered daily to patients with premalignant lesions for 3 months without overt toxicity (4).
The aims of the study described here can be divided into three broad categories. Firstly, we sought to analyze in detail the toxicity of high doses of curcumin administered orally to patients with advanced cancer. Expanding the reported data from the only published trial of doses >1.5 g daily in humans (4), we aimed to make this assessment by clinical parameters, quality-of-life questionnaire, and hematologic/biochemical tests. Secondly, we aimed to investigate the systemic effects of curcumin consumption. On the basis of our data from preclinical studies in models of colorectal carcinogenesis and in blood from healthy volunteers, we selected three biomarkers for translation into early clinical trials of curcumin on account of their relevance to carcinogenesis and the magnitude of change in response to treatment (9, 10, 11, 13). The three indices of the potential pharmacological activity of curcumin measured in patient blood leukocytes were: GST activity, levels of a deoxyguanosine adduct (M1G) formed via oxidative DNA damage, and inducible prostaglandin E2 (PGE2) levels as an indicator of COX-2 activity induced ex vivo by lipopolysaccharide (LPS). GST enzyme activity has been shown to be up- or down-regulated in rat tissues after oral consumption of curcumin, depending on the dose and route of administration (6, 7, 9). M1G levels are related to lipid peroxidation and oxidative stress and can be altered by feeding rats curcumin in their diet or by dietary modification in human volunteers (9, 14). Curcumin down-regulates COX2 transcription in human-derived colon cells (10). When added in vitro to blood from healthy volunteers, curcumin (1 μmol/L) reduced LPS-induced COX-2 protein levels and concomitant PGE2 production by 24% and 41%, respectively (11). The third aim of this Phase I study was to test the hypothesis that curcumin or products of its metabolism can be detected in blood or excreta of humans using high-performance liquid chromatography (HPLC) with UV detection and tandem quadrupole mass spectrometry (MS; refs. 13, 15).
Overall, the study was designed to define pharmacokinetic and pharmacodynamic parameters, which might help to optimize the clinical evaluation of curcumin in Phase II chemoprevention or chemotherapy trials.
The trial and formulation were approved by the local ethics committee and the United Kingdom Medicines Control Agency. Fifteen patients with histologically proven adenocarcinoma of the colon or rectum, for which no additional conventional therapies were available, met the following eligibility criteria: measurable or evaluable disease; age >18 years; WHO performance status of 0 to 2 and life expectancy >12 weeks; absolute neutrophil count ≥1.5 × 109/L; hemoglobin ≥10 g/dL; platelets ≥100 × 109/L; aspartate aminotransferase and alanine aminotransferase <2.5 times the upper limit of normal; serum bilirubin and creatinine <1.5 × upper limit of normal; and no previous investigational or chemotherapeutic drugs within 28 days before enrolment. Exclusion criteria included: active chronic inflammatory or autoimmune disease; active infection, including viral infection; significant impairment of gastrointestinal function or absorption; active peptic ulcer disease; known biliary obstruction or biliary insufficiency, and use of nonsteroidal anti-inflammatory drugs within 14 days of enrolment. They were enrolled between December 2000 and December 2002 at the University Hospitals of Leicester. Patients were asked to abstain from nonsteroidal anti-inflammatory drug use and the consumption of foods containing the spice turmeric during the study period, and their general practitioners were asked not to prescribe nonsteroidal anti-inflammatory drugs. Written informed consent was obtained from each patient before enrolment. Demographic and baseline characteristics of patients are shown in Table 1. All of the patients were white Caucasians except for 1 patient at the second dose level who was Indian.
Formulation, Dose, and Study Design.
"C3" curcuminoid capsules were provided in a single batch by the Sabinsa Corporation (Piscataway, NJ). Each capsule contained 500 mg of curcuminoids (450 mg of curcumin, 40 mg of desmethoxycurcumin, and 10 mg of bisdesmethoxycurcumin), confirmed by HPLC/MS. This formulation, which in the following text will be referred to as "curcumin," was selected on account of its reproducibility of curcuminoid content and the curcumin dose, which allowed rapid dose escalation from the highest doses administered previously to patients with cancer. All of the capsules of a daily dose were consumed together with water in the morning after at least 2 hours of fasting. Dependent on dose level, patients consumed 1, 2, 4, or 8 capsules (containing 450, 900, 1800, or 3600 mg of curcumin) once daily, as shown in Table 1. The highest dose level was defined as the dose at which plasma levels of curcumin were detected or any pharmacodynamic effects were observed. Treatment was continued until disease progression was established or consent was withdrawn.
Clinical Measurements.
Blood, urine, and feces were collected on days 1, 2, 8, and 29, protected from light and stored at −80°C. Blood collection was predose and at 0.5, 1, 2, 3, 6, and 8 hours after dose, and samples were kept in tubes pretreated with lithium-heparin (Sarstedt, Loughborough, United Kingdom). Full blood cell count and urea, electrolytes, liver, and bone function were measured in venous samples, and physical examination was performed, before treatment and on treatment days 1, 2, 8, 29, and monthly thereafter. Serum levels of total cholesterol and the tumor markers carcinoembryonic antigen, CA19.9, and CA125 were measured before treatment and every month of treatment. Blood samples for analysis of GST activity and M1G levels were collected 1 week before and on days 1, 2, 8, and 29 of treatment, immediately before dosing for M1G or immediately before and 1 hour after each dose for GST. Lymphocytes were separated from fresh blood using Ficoll-paque Plus (Amersham Pharmacia Biotech, Bucks, United Kingdom), resuspended in 1 mL of 10 mmol/L Tris-HCl (pH 7.8) and stored at −80°C. Patients completed the European Organization for Research and Treatment of Cancer quality of life questionnaire GLQ-C30 (version 2.0) pretreatment and monthly during treatment (16).
Patients were evaluated for tumor response every 8 weeks, using computed tomography or magnetic resonance imaging scanning, in addition to monthly chest X-rays. Measurements were made using the WHO Solid Tumor Response Criteria. All of the measurable, evaluable, and nonevaluable lesions were accounted for in the tumor assessment. Measurable lesions were quantified by the sum of the products of perpendicular diameters. Partial response was defined as at least a 50% decrease in the sum of the product of the perpendicular diameters of measurable lesions from baseline and with no development of new lesions. Progressive disease was defined as at least a 25% increase, clear worsening from previous assessment of any evaluable disease, reappearance of any lesion which had disappeared, or appearance of any new lesion/site. Stable disease was defined as the scenario in which the disease status had neither responded to meet the partial response criterion nor progressed to meet the progressive disease criteria.
Pharmacodynamic Assessments.
Glutathione and 1-chloro-2,4-dinitrobenzene were purchased from Sigma (Poole, United Kingdom). Once thawed, lymphocyte samples were sonicated for 30 seconds (Fisher 550 sonicator, Pittsburgh, PA) on ice and centrifuged at 3,000 × g (15 minutes, 4°C). Total GST activity in the supernatant was measured spectrophotometrically using glutathione and 1-chloro-2,4-dinitrobenzene as substrates in triplicate for each sample (17). Results were corrected for protein levels using the Bio-Rad protein assay (Bio-Rad, Hemel Hempstead, United Kingdom). The GST activity values were quoted as nanomole 1-chloro-2,4-dinitrobenzene conjugated with glutathione per minute per milligram of lymphocytic protein. The GSTM1, GSTT1, and GSTP1 genotypes were determined by PCR methods described previously (18, 19, 20). Murine M1G monoclonal antibody D10A1 was prepared as described previously (14). Antirabbit and antimurine horseradish peroxidase antibodies were purchased from Dako (Ely, United Kingdom). M1G standards were synthesized and characterized, genomic DNA was extracted from whole blood, and leukocytic M1G adduct levels were analyzed by immunoslot blot in triplicate as described previously (9, 13, 14). Discrepancies in the amount of DNA per slot were corrected for by staining the nitrocellulose filter with propidium iodide and performing UV light densitometry (9, 13). The detection limit for M1G was 5 adducts per 108 nucleotides. Blood was also taken for assessment of plasma PGE2 concentration induced ex vivo as reported previously (11).
Measurement of Curcumin and Its Metabolites.
Extraction of curcumin and its metabolites (curcumin glucuronide and curcumin sulfate) from plasma, urine, and feces; agent and metabolite recovery; and details of the reverse-phase HPLC (UV-visible detection) analysis were as described previously (13, 15). Retention times of curcumin glucuronide, curcumin sulfate, and curcumin were in general 24, 31, and 37 minutes respectively. The limit of detection for curcumin in plasma and urine was 5 pmol/mL. In most chromatographic analyses performed, curcumin and its conjugates were detected at levels that were close to the limit of quantitation. Quantitation was performed with a standard curve but without an internal standard and is, therefore, referred to as "semiquantitation." Interday variation of the assay for curcumin was 7.0%. Results are presented as mean ± SD.
The identities of curcuminoids and their metabolites in urine and plasma were verified using an Agilent 1100 series HPLC with in-line Applied Biosystems/MDS SCIEX API 2000 ion spray tandem quadrupole MS. Separation of curcuminoids and their metabolites was achieved using an HPLC method published previously (13, 15). Identification of compounds was achieved by MS in negative ion mode. Compound-specific fragmentation was detected using multiple reaction monitoring to identify curcumin and curcumin glucuronide (m/z 367 to 134 transition), desmethoxycurcumin and desmethoxycurcumin glucuronide (m/z 336 to 119 transition), and curcumin sulfate (m/z 447 to 367 transition).
Statistical Evaluation.
Results were subjected to ANOVA and linear regression analysis using Minitab (version 13) and SPSS (version 11.0) software packages. Plots of residuals were used to ensure that variances were homogeneous and that the residuals had a normal distribution. Comparison of samples taken immediately before dosing and 1 hour after dose was performed by paired t test for individual values, with Bonferroni adjustment for pair-wise comparisons between group means, and by repeated measures ANOVA for pooled measurements. Degrees of freedom (df) are stated for all of the results with P < 0.05.
Tolerability of Oral Curcumin.
Curcumin was well tolerated at all of the dose levels, and dose-limiting toxicity was not observed. Two types of gastrointestinal adverse events were reported by patients, which were probably related to curcumin consumption. One patient consuming 0.45 g curcumin daily and one patient consuming 3.6 g curcumin daily developed diarrhea (National Cancer Institute grades 1 and 2) 1 month and 4 months into treatment, respectively. In the first case, diarrhea was controlled with 4 mg of loperamide hydrochloride daily. The other patient withdrew consent from the study before the cause of the diarrhea could be investigated, which resolved after cessation of treatment. One patient consuming 0.9 g curcumin daily experienced nausea (National Cancer Institute toxicity grade 2), which resolved spontaneously despite continuation of treatment. Two abnormalities were detected in blood tests, both possibly related to treatment: a rise in serum alkaline phosphatase level was observed in 4 patients, consistent with National Cancer Institute grade 1 toxicity in 2 patients and grade 2 toxicity in 2 patients; serum lactate dehydrogenase rose to >150% of pretreatment values in 3 patients.
Biological Effects of Oral Curcumin.
Blood was taken immediately predose or 1 hour postdose on days 1, 2, 8, and 29. Whole blood was incubated for 24 hours in the presence of LPS (10 μg/mL). Oral administration of curcumin did not impact on basal PGE2 levels in leukocytes nor did doses of 0.45 to 1.8 g daily alter LPS-induced PGE2 (result not shown). However, consumption of 3.6 g of curcumin daily affected LPS-induced PGE2 levels (Fig. 1). When values obtained immediately pre- or 1 hour postdose on days 1, 2, 8, and 29 were pooled for the 6 patients consuming this dose, PGE2 levels observed postdose (3.2 ± 2.2 ng/mL) were significantly lower (46%, P = 0.028; df = 59) than those measured immediately predosing (4.5 ± 3.4 ng/mL). As shown in Fig. 1, the difference reached significance on day 1 (62% reduction, P < 0.05; df = 13) and day 29 of treatment (57% reduction, P = 0.01; df = 14). Subset analysis revealed no difference between inducible PGE2 levels in samples from the 3 patients in which curcumin was detected compared with those in which curcumin was not detected (see below). These results suggest that consumption of 3.6 g of curcumin daily is linked with inhibition of PGE2 induction in blood taken postdose compared with blood taken predose. Overall time-dependent trends were not identified at any dose in basal or LPS-stimulated PGE2.
Total GST activity and M1G levels in leukocytes differed substantially between patients with reasonable reproducibility for each patient across the 4-week study period, as borne out by average coefficients of variation within each patient of 15% and 31% for GST and M1G, respectively (data not shown). Treatment-related effects were not observed. Patients were genotyped for GST isoenzymes GSTM1, GSTP1, and GSTT1. Sixty percent of the patients lacked GSTM1. In patients who displayed null genotype for GSTM1, predose levels of leukocytic M1G (pooled for all time points) were 4.4 ± 0.7 per 107 nucleotides, 63% higher than those in patients expressing GSTM1, in whom adduct levels were 2.7 ± 1.1 per 107 nucleotides (P < 0.001; df = 30).
Levels of Curcumin and Its Metabolites in Blood and Excreta.
Curcumin was detected in plasma samples taken 0.5 and 1 hour postdose (see Fig. 2,A) from 3 patients consuming 3.6 g of curcumin daily. Semiquantitation afforded the mean of 11.1 ± 0.6 nmol/L for these 3 patients at the 1-hour time point on day 1, and curcumin levels were similar at the 1-hour time points on days 2, 8, and 29 of intervention. The maximum intrasubject variation of plasma curcumin at the 1-hour time point on days 1, 2, 8, and 29 of intervention was 24% of the mean from day 1. Intersubject variation of plasma curcumin at the 1-hour postdosing was between 7% and 41% of the respective means on days 1 and 29 of intervention, respectively. Curcumin was infrequently detected in the plasma of these patients at other time points, and it was not found in plasma from patients who received lower doses of curcumin. The curcumin formulation used contained small amounts of desmethoxycurcumin and bisdesmethoxycurcumin, which explained the two peaks at retention times slightly longer than curcumin shown in Fig. 2 A (panel iii). Glucuronides and sulfates of curcumin and desmethoxycurcumin were found in the plasma from all 6 of the patients consuming 3.6 g of curcumin daily at all of the time points studied. The presence in plasma of curcumin, desmethoxycurcumin, and their glucuronide and sulfate metabolites was confirmed by MS. Semiquantitation of levels in pooled plasma samples yielded 8.9 ± 0.7 and 15.8 ± 0.9 nmol/L for curcumin sulfate and curcumin glucuronide, respectively. There were no obvious differences in the levels of these conjugates when plasma samples from the 3 patients in which curcumin was detected were compared with those in which curcumin was not detected.
Analysis of urine suggested the presence of curcumin and the conjugates in all of the samples from patients consuming 3.6 g of curcumin daily (Fig. 2,B). Such chromatographic peaks were not seen in any extracts of urine samples from patients on the lower doses. In the 6 patients consuming 3.6 g of curcumin daily, urinary levels varied between 0.1 and 1.3 μmol/L (curcumin), 19 and 45 nmol/L (curcumin sulfate), and 210 and 510 nmol/L (curcumin glucuronide; see Fig. 2,B and Fig. 3). On the basis of the preclinical data currently available, the presence of curcumin and its metabolites in the urine was unexpected. Therefore, the assignment of HPLC peaks to structures was confirmed by cochromatography using authentic standards and corroborated by MS with multiple reaction monitoring. These techniques demonstrated the presence of curcumin and curcumin glucuronide, desmethoxycurcumin and desmethoxycurcumin glucuronide, and curcumin sulfate by compound-specific fragmentation (Fig. 4). Abundant amounts of curcumin were recovered from the feces (Fig. 2 C) at all of the dose levels. Curcumin levels in day 8 fecal samples from patients consuming 3.6 g of curcumin daily were between 25 and 116 nmol/g dried feces. Fecal levels of curcumin did not correlate with toxicity in the 2 patients who experienced diarrhea. Trace amounts of curcumin sulfate were detected in feces from 3 patients consuming 3.6 g of curcumin daily.
Effects of Oral Curcumin on Malignancy.
All of the patients enrolled exhibited radiologic evidence of progressive disease before recruitment. No partial responses to treatment were observed. Two patients exhibited stable disease by radiologic criteria after 2 months of treatment, and they remained on treatment for a total of 4 months. The first of these 2 patients (dose level 2) developed progressive disease on her second computed tomography scan. The other patient (dose level 3) demonstrated continued stable disease on computed tomography scan after 4 months, but she withdrew consent on account of diarrhea, which she thought was treatment-related. Decreases in tumor markers or serum cholesterol were not observed as a result of treatment in any of the patients. Three significant changes in quality of life scores were recorded: 1 patient noticed a significant improvement after 1 month of treatment; and 2 patients deteriorated after 2 months of treatment, both of whom were found to have radiologic progressive disease.
The study presented here provides the first report of the systemic parameters of pharmacokinetics and activity of curcumin that are likely to be of value in Phase II chemoprevention/anticancer trials of this agent. The results permit the following three conclusions to be drawn regarding oral curcumin in humans: (1) administration of 0.5 to 3.6 g daily for up to 4 months is associated with mild diarrhea as its only discernible toxicity, (2) consumption of 3.6 g of curcumin daily generates detectable levels of parent compound and conjugates in plasma and urine, and (3) consumption of 3.6 g of curcumin daily causes inhibition of PGE2 production in blood leukocytes measured ex vivo. These conclusions lead us to propose that an oral dose of 3.6 g daily is suitable for evaluation in Phase II trials.
The observed safety of curcumin is consistent with previous reports of clinical studies of curcumin and Curcuma extracts (4, 13, 21, 22). Cheng et al. (4) treated patients with premalignant conditions with tablets containing pure curcumin for up to 3 months. The authors did not record any treatment-related toxicity at daily doses as high as 8 g, although quality of life was not measured, and blood results were not presented. Levels of curcumin observed at the 1-hour time point after a dose of 3.6 g in the study described here are ∼1/40 of those described by Cheng et al. (4) when they administered 4 g of curcumin. The reason for the discrepancy between the two studies is unclear; it may be associated with the fact that the formulation used by Cheng et al. (4) consisted of pure chemically synthesized curcumin, whereas the formulation used in the trial described here was composed of a purified turmeric extract containing 10% curcuminoids other than curcumin (see Patients and Methods).
Our second conclusion is that consumption of 3.6 g of oral curcumin daily results in levels of drug and conjugates in plasma near the limit of detection of the assays used. Low systemic bioavailability after oral dosing is consistent with findings in preclinical models (9, 12, 23) and in humans (4, 13, 21, 22). In our laboratory, the adenoma-suppressing activity of dietary curcumin (0.2%, equivalent to ∼300 mg/kg per day) in the APC Min mouse model was associated with a mean level of 111 nmol/g curcumin in the mucosa of the small intestine (23). The curcumin concentration in the plasma of these mice was close to the limit of detection (5 pmol/mL), irrespective of the dietary doses (0.1%, 0.2%, and 0.5%) studied. This result suggests that intestinal mucosal levels of curcumin may not be reflected by its systemic levels. Efficient metabolism of curcumin, especially glucuronidation and sulfation, may explain its poor systemic availability when administered via the oral route (4, 13, 15) and is compatible with the finding of metabolites in the plasma of all of the patients consuming 3.6 g daily, although parent compound was detected in the plasma of only half of the patients consuming this dose. Measurement of compliance is increasingly perceived to be an important component of intervention trials (24). The consistent presence of curcumin and its conjugates in urine observed here in patients consuming 3.6 g of curcumin daily is of relevance to the potential clinical advancement of curcumin as a chemopreventive agent. Urinary analysis of drug-derived species constitutes an easily accessible and reproducible test for ensuring general compliance.
Of the three potential biomarkers of the systemic activity of curcumin explored in this study, levels of M1G and GST were unaffected by curcumin. These results indicate that leukocyte M1G and GST are not useful indicators of the systemic activity of curcumin in humans due to lack of effect at the low systemic levels of curcumin that result from oral dosing. Interestingly, consistent with a previous observation in patients with advanced colorectal cancer (13), those who lacked GSTM1 expression, a common phenotype in Caucasian populations, had higher leukocyte M1G levels than GSTM1-expressing patients. Although GST-μ is not the most abundant of the GST isoenzyme classes expressed in human lymphocytes (19, 20), this observation suggests that lack of GSTM1 activity may be of direct relevance to the detoxification of endogenous and exogenous oxidants, which cause modification of bases in DNA.
In contrast to M1G and GST, the inducibility of PGE2 production in whole blood ex vivo may represent a useful tool for assessing the systemic activity of curcumin. COX-2 is an important pharmacological target for nonsteroidal anti-inflammatory drugs, selective COX-2 inhibitors, and polyphenolic agents derived from the diet (25). Because COX-2 is thought to play a pathogenic role in the carcinogenesis of many tissues, its pharmacological modulation holds implications for cancer prevention and treatment (11, 25). Previous work in our laboratory on the assay described here suggested that at least part of the effect of curcumin on inducible PGE2 production in human blood can be attributed to inhibition of COX2 transcription (11). This phenomenon was also observed in human-derived colon cells cultured in vitro, and inhibition was demonstrated to be the corollary, at least in part, of the inhibition of the nuclear factor-κB–activating enzymes IKK-α/β by curcumin (10, 15). A mechanism analogous to that described in colon cells in vitro may operate in human leukocytes exposed to curcumin. Remarkably, the effect of curcumin described here was associated with plasma levels detected in the 10−8 mol/L range, less than a hundredth of the concentration of curcumin shown in vitro to elicit an effect in blood or colon cells (10, 11, 15). Frustratingly, experiments designed to study the effect of submicromolar concentrations of curcumin in cells in vitro were limited by the inhibitory activity of the solvent (dimethyl sulfoxide) on PGE2 production (11). The finding that a difference between predose and postdose was not observed on days 2 and 8 of treatment demonstrates the limitations of this assay as a biomarker of activity on account of the high interday intraindividual variation. Therefore, we suggest that incorporation of this biomarker into Phase II clinical trials of curcumin should use multiple time points and a specified minimum cohort size to account for this variability in the power calculations. Measurement of PGE2 levels may be considered in target tissue as a biomarker that may reflect potential anticancer activity and in blood as an indicator of systemic activity and as a potential "surrogate" for the target tissue.
It should also be noted that curcumin sulfate and products of metabolic reduction of curcumin also inhibited PGE2 production in colon cells in vitro, although their inhibitory potency appeared lower than that of parent curcumin (15). Interestingly, some studies have suggested that curcumin elicits systemic effects relevant to the chemoprevention of cancer in hepatic and mammary tissues of animals, despite attainment of levels of curcumin in these tissues that are in the 10−9 to 10−8 mol/L range (26, 27).
The optimization of Phase I clinical trials of diet-derived putative chemopreventive agents in patients with advanced solid tumors is currently under development in recognition of the fact that the molecular targets of chemoprevention and chemotherapy are often similar or identical (28). Results from pilot studies, such as the clinical trial described here or recent reports on green tea extract (29) or soy isoflavones (30), demonstrate the feasibility of measuring potential biomarkers of pharmacodynamic effects in addition to assessment of toxicity and pharmacokinetics. Such data improve the planning process for Phase II trials in the prevention or treatment of cancer.
The longstanding general view that the "point of failure" for the clinical development of oral curcumin as an agent directed at the prevention or therapy of cancer in tissues outside the gastrointestinal tract will be its low systemic bioavailability should be reviewed in light of the results presented here. Definite conclusions regarding the optimum dose for targeting the gastrointestinal mucosa cannot be drawn from the study presented here; a separate dose de-escalation trial has been conducted recently in patients with resectable cancers based on the assumption that doses <3.6 g daily may be efficacious. The findings of the study presented here lead us to conclude that the systemic pharmacological properties of a daily dose of 3.6 g of curcumin are suitable for its evaluation in the prevention of malignancies at sites other than the gastrointestinal tract.
Grant support: University Hospitals of Leicester, the Association for International Cancer Research, and the United Kingdom Medical Research Council.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Requests for reprints: Ricky Sharma, Radiotherapy Department, Royal Marsden Hospital, Sutton, SM2 5PT, United Kingdom. Phone: 44-208-642-6011; Fax: 44-116-223-1855; E-mail: firstname.lastname@example.com
We express our gratitude to the patients who participated in the study, Sabinsa Corporation for providing C3 capsules, Profs. D. Barnett and P. Woll for reviewing the case report forms, and Dr. M. Manson and Prof. D. Brenner for detailed reviews of the manuscript. We thank Sue Spriggs, Jo Arden, and Clare Winfield for secretarial assistance.


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Analysis of Techniques for Measuring Carrier Recombination Lifetime
Published on
Rapid, accurate and contactless measurement of the recombination lifetime is a very important activity in photovoltaics. The excess carrier lifetime (Δn(t)) is the most critical and variable parameter in the development of photovoltaic materials. Device performance can be accurately predicted from the lifetime measurement of the starting material. However, there is no single measurement that directly measures the bulk lifetime as all measurements are based on a device model.
A primary issue is that the lifetime is a function of excess carrier lifetime, and measurements must be linked to an injection level. The most common measurements are based on either photoconductive (PCD) or photoluminescence (TRPL) decay. PC decay senses the product of excess carrier concentration (Δn) and mobility (μ (Δn)). This mobility variation must be included in order to extract the true excess carrier lifetime. TRPL works best for direct band gap materials and therefore is not applicable to silicon. For polycrystalline materials, shallow traps distort the measurement and must be included in the analysis of the data. Finally, surface and interface recombination have profound influence on most measurements and must be minimized for accurate measurement of the true bulk lifetime.
Both techniques and analysis methods will be discussed in this seminar. Typical sample measurements will be shown, including representative thin film and wafer materials that are currently popular in the photovoltaic community.
Dr. Richard K. Ahrenkiel is a Research Professor of Metallurgical and Materials Engineering at the Colorado School of Mines in Golden, Colorado. He is also a Consultant and Research Fellow Emeritus at the National Renewable Energy Laboratory (NREL), where he worked from 1981 to 2005. Prior to NREL, he worked at Eastman Kodak Research laboratories, and at the Los Alamos National Laboratory. Dr. Ahrenkiel's area of specialization is the measurement and characterization of photovoltaic cells and materials, and he is one of the world experts in the area of carrier recombination and carrier lifetime. He invented a unique technique for measuring the excess carrier lifetime in materials. This technique, named Resonance-coupled photoconductive decay (RCPCD), has been extensively applied to silicon and non-silicon materials. Dr. Ahrenkiel received a B.S. degree in Engineering Physics and his M.S. and Ph.D. degrees in Physics at the University of Illinois, Urbana.
Sponsored by
npt (Network for Photovoltaic Technology), ncn (Network for Computational Nanotechnology), Discovery Park
Cite this work
Researchers should cite this work as follows:
Birck Technology Center, Room 1001, Purdue University, West Lafayette, IN

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The Lateral Assistance Program is available to assist homeowners who have to replace a deteriorated sewer service line and partially cover the cost of work done within the public right of way. Please note that as a requirement of this program, residents must:
Click on the link above for specific program guidelines. Residents may also call 311 for program information.


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Myers named AL Rookie of the Month
Two-homer game, eight-game hit streak among slugger's September highlights
Wil Myers' chase for the American League Rookie of the Year Award received a boost Monday when the Rays outfielder was named AL Rookie of the Month for September.
"I'm not concerned about [the Rookie of the Year Award]," Myers said on Monday. "I'm more concerned about today. It's the last game of the season -- regular season -- and everybody's got to come out and play hard, and I think everyone's a little more amped for this game. So we just have to go out and play our game. Whatever happens, happens."
Myers hit .317/.360/.558 with 13 doubles and four home runs in 27 games to help the Rays advance to Monday's AL Wild Card tiebreaker against the Rangers.
"If you can help the team out in September, I think that's the biggest thing," he said.
The 22-year-old finished first among rookies in hits (33), runs (18), doubles, extra-base hits (17) and total bases (58), while tying for first in homers. He also ranked second in RBIs, batting average, on-base percentage and slugging percentage.
Myers notched his second career multi-homer game Sept. 4 against the Angels and put together an eight-game hitting streak from Sept. 11-18, during which he batted .387 with five doubles, two homers and seven RBIs.
He was 2-for-4 with two doubles and drove in a run in Sunday's finale to help the Rays advance to the tiebreaker game.
Myers is the second Rays rookie to earn monthly honors this season following Chris Archer's July award and is the first Rays position player to win the award since Evan Longoria in June 2008.


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Anne Ayres Biography
Anne Ayres
Protestant nunBorn: Jan. 3, 1816
Birthplace: London, England
Ayres came to the United States in 1836 and settled in New York City. She worked as a governess until 1845, when she decided to pursue a life of service to God. At the time, there were no established religious orders for Protestant women in the American Episcopal Church or in the Church of England, so Ayres was consecrated a "sister of the Holy Communion" by Dr. William Augustus Muhlenberg, an Episcopal clergyman. After a few other women joined Ayres in running a parish school and working with the poor, they were formally organized as the Sisterhood of the Holy Communion in 1852, with Ayres as First Sister. The sisters, who made renewable pledges of service instead of taking permanent vows, opened an infirmary in 1853. Later they moved to St. Luke's Hospital, where Ayres directed the housekeeping and nursing. Ayres was also instrumental in opening St. Johnland, a refuge for the poor and disabled on Long Island.
Died: Feb. 9, 1896


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Museums and Biographies: Stories, Objects, Identities
edited by: Kate Hill
London, Boydell and Brewer, 2012, ISBN: 9781843837275; 348pp.; Price: £60.00
Nottingham Trent University
Date accessed: 28 February, 2024
Slowly but surely the history presented in museums is coming to the attention of academic historians. However, the relationship between museums, memory and history remains complex. In selecting what to collect, museums seek to define what is or is not history. In preserving their collections in perpetuity they act as a permanent, if selective, memory store. In the way they display and interpret that material evidence, they construct and transmit meanings. In contemporary museum display, there is an on-going conflict between the construction of meanings that support an authorised collective memory, frequently linked to a linear narrative of progress, and an ambition to act as places of pluralism and inclusion. Furthermore, visitors to museums are not passive recipients. Rather, in the process of engaging with the collections and associated interpretive material on display, visitors add new content to their existing knowledge and understanding, and construct their own meanings. History is thus selected, constructed and transmitted by museums and then, in the process of being experienced by visitors, it is transformed into 'something else – their own understanding of the past, a type of 'historical sense' independent of the professional historian's ideal …'.(1) For the academic historian new to the debate on what makes history in museums, the variety of content, particularly in the latter half of this edited volume, gives some sense of the complexity of the subject. There is much of interest that can also be garnered from the first part, not least in considering how museums and their collections came into being.
The book weighs in at two pounds four ounces, but is heavyweight also in its content, '... the many finely articulated and challenging contributions to this rich collection of observations on museums and biography', as Preziosi describes them in his endpiece (p. 321). It is based on a conference of the same title, held in 2009 under the auspices of the Museums and Galleries History Group, itself founded in 2002 'to promote the study of the history and theory of museums and galleries' (www.mghg.org). The website states that the Group 'acts as a forum for considerations of the place of museum history within academic discourse and its importance for current museum practice'. This dual ambition is evident throughout much of the 325 pages of text of the book, consisting of an introduction and endpiece, and 21 chapters positioned under six sections as a reflection of the breadth of approaches taken, and supported by 51 illustrations.
In her introduction the editor, Kate Hill, sets the challenge: '... to consider how biography in and of the museum can be used to become more reflexive about the 19th-century inheritance [the 19th-century museum's concern to develop an objective, systematic representation of the world as knowable by the Western subject], and to develop new ways of knowing' – no mean feat if achieved. The central structure of the book is defined by its six sections. 'Individual biography and museum history' 'investigates the extent to which individuals have been identified with particular museums, and have even "become" their museum in some ways'. 'Problematising individuals' biographies' '... takes issue with the extent to which simple and discrete life stories of individual selves can explain museums and their histories'. 'Institutional biographies' '... aims to examine the extent to which the institution of the museum itself has a biography'. 'Object biographies' '... brings together a number of essays which are interested in using the object biography approach to understand museums more fully'. 'Museums as biography' '... assesses the ways in which museums can produce biographical narratives'. Finally, 'Museums as autobiography' '... interrogates the ways in which museums can enable people to tell their own lives in different ways and for different groupings'.
The three chapters in the first section examine benefactors to the Cabinet des médailles et antiques in Paris, and the impact of two curators on their institutions – Hultén at Sweden's Museum of Modern Art and Pavière at the Harris Museum and Art Gallery, Preston. What surprised me about much of Gray's account of Pavière's work in Preston was how contemporary many of his ambitions were, not least for the museum to play an active role in the cultural life of Lancashire and for the visitor to be the central focus of the museum. By contrast, Burch's chapter on Hultén was undoubtedly the most troubling of the book, as he explored '... the pervasive influence that certain individuals are able to exert over public collections – both during their lifetime and after' (p. 29). The lesson Burch drew from his account is one we should all note: '... the paramount necessity of maintaining a critical eye on museums and the people and organisations that shape them' (p. 42).
In the section on 'Problematising individuals' biographies', it falls to Anne Whitelaw to challenge the whole premise of the book: 'In the specific case of the museum, biography's focus on individuals risks isolating particular figures from the larger institutional structures that shape their activities, and the linear character of its narrative does not account for the complexity of the institution itself, particularly as it pertains to the relations between individuals and the roles they inhabit' (p. 76). She illustrates this in her chapter on 'Women, museums and the problem of biography' in speaking of the privileging of those in leadership roles, '... at the expense of uncovering the anonymous, often collective labour of other women working in museums' (p. 80). Her concluding remark is: 'Given the complexity of the institution and the imbrications of its practices with the people – both known and unknown – who contribute to their realisation, biography is inadequate to the task' (p. 85).
By contrast, Sandino, in researching the professional lives of Victoria and Albert Museum curators, is able to argue strongly in favour of the biographical approach, placing the curators within the realms of collective memory, wonderfully borrowing from Nora to propose the community of long-term curators as a lieu de mémoire: '... a community that bears comparison with any village made up of a mixture of personalities, competencies, gossip, surveillance, alliances and disagreements but bound by a commitment to a particular sense of place' (p. 91). Thus, just as we see museum collections as the cultural memory of humankind, if a selective one, so she sees the curators as an 'active repository of memory' (p. 91), based on their lifelong interaction with those very collections.Five chapters explore aspects of 'Institutional biographies' – a very contemporary issue, given the unprecedented wave of new museum developments that took place in the late 1990s and 2000s. Janes, quoted in the first chapter in the section, has been particularly critical of this:
Although often likened to a renaissance, this architectural boom doesn't merit this praise, lacking as it commonly does any vigorous intellectual or creative resurgence within the museum itself.(2)
MacLeod, author of the first chapter in the section, is right to state that we need to establish what we have learned from this phase, not least because 'The sole focus on the architect and architectural style neglects any consideration of the needs of multiple users of the museum and promotes the desire among patrons and funders for a signature building by a named architect' (p. 106) – nothing new there then. Comparing this to past experiences is one approach. Her example is the prolonged gestation period of the Walker Art Gallery in Liverpool.
The other chapters see Miller explore the complex history of Schinkel's museums in Berlin, Apt examine the impact of the use of incorporation in the establishment of non-profit museums in the USA, Rees Leahy evaluate a recent spate of attempts to re-create past exhibitions and Whitehead discuss the 'restoration' of the Barry Rooms in the National Gallery in London, in the 1980s. With the National Gallery, Whitehead begins with the, as he puts it, very basic point that 'museum buildings represent attitudes to knowledge specific to the cultures which give rise to them' (p. 157). So he shows how the original Victorian Barry rooms were later modernised as neutral spaces, in a 'reaction against old-fashioned ways of looking at, understanding and experiencing art' (p. 158), but there was then a significant about face in the 1980s and 1990s, resulting in a series of costly restoration projects nationally, reflecting new developments in museum studies and art history. Both Whitehead and Rees Leahy highlight the basic problem however, '... the fallacy of authenticity at play' (p. 166). Visitors do not see the displays as they would originally have been. The dilemma, as Whitehead puts it, is that '... museums present themselves on the one hand as historical institutions which prize their own history... and, on the other, as constant re-inventors of themselves ...' (p. 167).
'Object biographies' is a very tight, thought-provoking section of four chapters, each exploring a different aspect of what used to be called ethnographic collections. We see the complex ways in which Chinese objects have been viewed and classified by the West over the last 150 years; the journey of a ritual red feather coat from 17th-century Brazil via the Netherlands to the Danish National Museum; the private development of a collection of Pacific artefacts; and the uncertainty felt by Cambridge Museum of Archaeology and Ethnography at its rediscovery of a collection of sculptures of Indian 'types', made in the 1930s, and accessioned into its collections in 1948 and 1951. The underpinning concept for the section relates theory directly to practice: the ability to present these objects in a way that will stimulate visitors to think more critically about them, and about the issues that underpin them.
In Tythacott's account of the Buddhist bronzes held by Liverpool Museum, we see an early wrestling over 19th-century racial hierarchies that placed the Western male at their summit – how to distinguish between Asia's 'highly cultivated' (3) races that were not a part of ethnology and the 'aboriginal races' that were – placing Chinese figures in a 'position somewhere between the 'civilised' white and the 'uncivilised black races' of the world' (p. 176). In Françozo's chapter on the red feather coat, we discover that, from feather adornments initially being produced for religious and war rituals, local populations in Brazil had begun from early in the colonial encounter to manufacture them for exchange with European colonisers and travellers. The sculptured heads of Indian 'types' were linked to a belief in the interconnectedness of physical characteristics and physiological or mental capacities. In Elliott's discussion, he notes that 'it is the disturbing connotations of colonial oppression, racial prejudice and the objectification of individuals into representatives of primitive tribes or other anthropological categories that has influenced the ambivalent reception of Milward's sculptures by postcolonial museum curators and academics' (p. 222).
For Françozo, speaking of the red feather coat, 'By simply looking at these items, one is confronted with the complexities of the colonial encounter that took place between Brazil and the Netherlands in the mid-17th century' (p. 196). Elliott, who displayed the Indian 'types' in 2009-10, believed their presence 'created a space to reflect upon more difficult and contentious periods in the history of the museum and of anthropology ...' (p. 226). The ability of museums to exhibit and encourage meaningful reflection on difficult issues is a major contemporary issue, requiring some visitor research to establish impact in both these cases.
'Museums as biography' are a relatively common phenomenon: 'Museums which are focused on a single personality are a popular sub-type of the museum genre, with over 170 in the UK alone, of which the birth-place museum is the best-known type' (p. 247). As the author of this chapter, Sophie Forgan, points out, next in popularity come artists and national heroes, while those on women or scientists form a tiny minority. Forgan briefly discusses the origins of three of the latter: Isaac Newton's birthplace at Woolsthorpe; Charles Darwin's Home at Down House in Kent; and the house in London where Sigmund Freud lived from 1938 to his death in 1939, 20 Maresfield Gardens in West Hampstead. She emphasises the importance of the passionate individual believer in the founding of such personality museums. Her focus is on what such museums can achieve and how this is done: '... presentation has to focus on the man (or woman) first and foremost; and the site, the house, its contents are seen as the key to unlocking personality. The purpose is threefold: to humanise the subject and create a sense of the person, to allow key objects to stand in for a long and complex 'whole life', and finally to provide models for inspiration and emulation ... The museum, like the best biography, has to attempt to re-integrate the personal and the scientific life, but in a very different genre' (p. 257). She is also very aware of the need to meet visitor needs: 'Personality museums have the problem of maintaining that indefinable quality called 'atmosphere', whilst at the same time attempting to diversify the visitor experience ... a sort of individualised consumption by the tourist' (p. 259–60). This is the potentially depressing part of her story – when theory meets practice – but I feel she has over-egged it a little. To make this case would require a detailed analysis of the motivations and expectations of actual visitors to personality museums.
Booth, in her chapter in this section, goes a stage further than Forgan in her discussion of the personality represented, quoting from Parker (4) that '... museum professionals should admit that "we are not simply in the business of preserving artifacts; we are also in the business of calling up ghosts" ... The biographical house museum is a house haunted in a way that echoes the readers' response to written lives in non-fiction as well as fiction' (p. 231–2). She sees such houses as lieux des memoires, but recognises how sanitised they can become. Yet the house and the objects in it – not least, for the writer, the scene of creativity with the study, desk, chair and pen – provide a public performance of the personality's life. Like Forgan, she recognises that the house experience will be audience driven: 'the audience constructs the house by re-reading it as inhabited'.
Coming to the final section, the concept of the 'Museum as autobiography' is at the heart of current thinking in history museums. It is part of an on-going response to the rise of the new social history in the 1960s and 1970s, and the influence of the writings of Bourdieu (5), leading to a call for the 'democratisation' of mainstream museums through the representation of multiple perspectives, social and cultural diversity, and reaching out to new communities. Today it reflects the replacement of the single, authoritative version of the past with a multivocal alternative. We see many museums working with those previously silenced, spoken for or marginalised to reclaim ownership of their own and their communities' pasts. In essence, it is about the democratisation of the past and the role museums can play in this. The trouble is that democratised history is messy in comparison with the more authoritative work of academic historians. How do you ensure the quality of the history presented?
The papers by Steffi de Jong and Elizabeth Crooke add to the debate. De Jong, exploring the incorporation of individual video histories into museum display, is excellent in her discussion of both the practical problems and the basic issue that the museum still retains authority in defining the interviewing process, in the selection of episodes from the life-story and the loss of individual identity as stories are used to illustrate themes chosen by the museum. By way of contrast, Crooke explores how communities research and tell their own stories as 'contributions to community autobiography' (p. 309). The community becomes its own author and censor. Crooke recognises the importance of this switch: 'The expectation of what history is, with whom it is concerned, the sources it draws upon and who should be its author has dramatically changed' (p. 311) – with academics and curators of recent history now 'indebted to the people on the ground' (p. 312). Crooke also recognises that communities will have different understandings and uses of the past than professional historians and will self-censor material that does not fit into the story they want to tell. Authority, identity and selectivity are all exposed in these two chapters and I would have relished more on each of these issues, and on the sheer messiness of democratic history.
So, does my account suggest the book is a useful collection of disparate accounts relating to aspects of museum history and practice or is the whole greater than the sum of the parts? As a practitioner who specialises in the development of content for museum exhibitions, I must focus on relevance to current museum practice. As the comments above make clear, the final two sections relate directly to practice while that on 'Object biographies' cries out for new, participative and reflective means of display that can draw out historical issues in ways that will make a meaningful difference to the attitudes of visitors. However, the chapters as a whole raise a more profound issue. In the 'age of participation' (6) in which we now live, museum users are no longer willing to be passive recipients of received wisdom, but are becoming more critical and challenging, and expect both to be able to contribute and to have their contributions valued. They effectively want a sense of ownership of what are public institutions, and museums must respond to this by becoming more transparent in all aspects of their activities, and more welcoming of user participation. The issue of transparency towards their users is present, if not always noted, in all of the essays in this volume. It is an issue that can only become more important.
- S. Watson, 'Myth, memory and the senses in the Churchill Museum', in Museum Materialities: Objects, Engagements, Interpretation, ed. Sandra H. Dudley (Oxford, 2010) pp. 204–23, p. 205, quoted in G. Black, 'Museums, memory and history', Cultural and Social History, 8, 3 (2011), 415–27, 415.Back to (1)
- R. R. Janes, Museums in a Troubled World (London, 2009), p.108.Back to (2)
- C. Gatty,Catalogue of the Mayer Museum II: Prehistoric Antiquities and Ethnography, (London, 1982).Back to (3)
- D. Parker, 'Literary museums: present opportunities', in Literary Memorial Museums, ed. W. Bartel and M. Kunze, M. (Frankfurt & Berlin, 1986), pp. 25–9.Back to (4)
- Pierre Bourdieu and Alain Darbel with Dominique Schnapper, The Love of Art: European Art Museums and their Public, trans. Caroline Beattie and Nick Merriman (Stanford, CA, 1969 (1990 ed.)).Back to (5)
- S. McNealy, Oracle Open World Keynote Speech, 20 September 2005 <reported in press release at http://news.cnet.com/2300-1010_3-5875466.html> [accessed 12 December 2012].Back to (6)
Author's Response
I would like to thank Graham Black for his detailed and useful review of Museums and Biographies. It is not an easy task to summarise and evaluate all 21 chapters, but he has done justice to the widely varying topics and approaches of the authors. While we have certainly sought to engage with the debates in current museum practice, we would not want the collection to be seen solely in that light – it is intended to help us think more widely about the nature of biography and narrative, as well as about the historical consciousness of different periods, places and individuals. In terms of current museum practice, I wholeheartedly agree with the reviewer that transparency is a key issue; for me, the process of editing the collection convinced me that transparency is very hard for museums to achieve. The complicated histories of the institutions, and the entrenched nature of their existing narratives, mean that real, meaningful transparency that allows ownership by the public can only be achieved through a painstaking, historically informed process of unpicking and de-naturalising the museum's constituent parts. I hope that Museums and Biographies is a contribution to that process.


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- News / Notre Dame student newspaper editor quits after anti-gay slur / Click here
- News / Notre Dame football coach Brian Kelly's religious, Catholic values questioned / Click here
The University of Notre Dame is being rocked by a controversy over an anti-gay cartoon printed in the student-run newspaper, The Observer.
The cartoon depicts a conversation between two figures that reads:
"What's the easiest way to turn a fruit into a vegetable?"
"No idea."
"A baseball bat."
Earlier, the cartoonist, who has not yet been named, posted the original version of the cartoon on his blog. In this version, it shows the punch line as "AIDS" instead of "a baseball bat." The paper, he claimed, preferred "not to make light of fatal diseases."
In a statement to the press today, The Gay and Lesbian Alliance Against Defamation (GLAAD) claimed "The Observer made a dangerously misguided decision that promoting violence was somehow superior to making fun of HIV/AIDS. Both versions of the cartoon were abhorrent."
GLAAD contacted The Observer's editor, Jenn Metz, who relayed a tearful apology by phone. She explained that she was not present when the decision to run the cartoon was made, and that she was incredibly upset that others on staff had made that decision.
An apology printed in the paper this morning included the following:
The editors of The Observer would like to publicly apologize for the publication of "The Mobile Party" in the Jan. 13 edition. The burden of responsibility ultimately lies on us for allowing it to go to print.
There is no excuse that can be given and nothing that can be said to reverse the damage that has already been done by this egregious error in judgment.
Allowing this cruel and hateful comic a place on our pages disgraced those values and severely hurt members of our Notre Dame family — our classmates, our friends. For this, we sincerely apologize. Unfortunately, the language of hate is an everyday reality in our society."


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The family of a U.S. Marine who committed suicide inside a U.S. Embassy in Greece says their son was buried without a heart, after the Greek government performed an illegal autopsy on his body and "harvested" the organ.
Craig and Beverly LaLoup, of Coatesville, Pa., filed a lawsuit in federal court on Friday against the U.S. Department of Defense, U.S. Navy and U.S. government for negligence, emotional distress and alleged mistreatment of their son's body.
U.S. Marine Sgt. Brian LaLoup, who was stationed at the U.S. Embassy in Athens, Greece, shot himself following a night out drinking in the Greek capital on Aug. 12, 2012, according to the court filing. The 22-year-old allegedly had been at an off-duty party when he told a fellow officer he was considering ending his life.
"I don't have anyone who loves me," he allegedly said. He then apparently told the officer he was planning to shoot himself in the face with a shotgun.
That officer notified a superior, listed in the suit as Staff Sgt. Martinez, about Brian's intentions. But instead of getting him medical care, the commander allegedly took him out to drink more – a violation of Marine Corps protocol, the lawsuit claims.
Later that night, Brian went into an unlocked room inside the embassy, where weapons were stored, and committed suicide. According to court documents, he was visibly drunk and distraught and passed a guard on his way through the building.
Brian was taken to an Athens hospital and pronounced dead. The family says his body was left unguarded and because of that, the body was moved to a Greek morgue where, several days later, an illegal autopsy was performed. It was during that autopsy that Brian's heart was removed, according to the complaint.
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The sergeant's body was flown back to the United States and upon arrival at Dover Air Force Base, a second autopsy was performed. The LaLoups say that's when officials realized the heart was gone. However, the family claims they were never told their son's heart was gone until after he was buried.
"Instead of being honest and up-front with the family and taking the appropriate action to have the heart returned, [the] Defendants decided to lie and conceal this fact from the Plaintiffs," the suit says. "As a result of Defendants' failure to act, Sgt. LaLoup's heart was destroyed by the Greek government."
According to the lawsuit, the family said they were told only parts of their son's scalp were missing and they didn't realize his heart was gone until after another officer told them "by accident."
"He extended to me a piece of paper as he stated it was his heart that was missing. I asked him why were we told it was parts of his scalp. His reply was, 'that they were not going to tell us because that is not something you tell a grieving mother,'" Beverly LaLoup stated in the filing.
After the LaLoups lodged complaints about the situation, the lawsuit claims the Greek government sent a heart they claimed was Brian's to the United States. However, DNA testing showed it was not his organ, according to the filing. The heart still remains missing.
The couple believes officials violated several protocols and intentionally lied to them about the missing heart, the suit states. They seeking damages in excess of $75,000.
A spokesman for the Department of Defense said on Monday that the department does not comment on litigation.
Chrisos Failadis, president of communications for the Greek Embassy in Washington, D.C., said they were unaware of the case. They have reached out to the country's minister on foreign affairs for more information on the allegations.
Contact Vince Lattanzio at 610.668.5532, firstname.lastname@example.com or follow @VinceLattanzio on Twitter.


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If you're a designer, entrepreneur, or creative — you probably haven't been asked for your resume in a long time. Instead, people Google you — and quickly assess your talents based on your website, portfolio, and social media profiles.
Do they resonate with what you're sharing? Do they identify with your story? Are you even giving them a story to wrap their head around?
Gone are the days of "Just the facts, Ma'am." Instead we're all trying to suss each other out in the relationship economy. Do I share something in common with you? How do we relate to each other? Are you relevant to my work?
That's why the resume is on the out, and the bio is on the rise.
People work with people they can relate to and identify with. Trust comes from personal disclosure. And that kind of sharing is hard to convey in a resume. Your bio needs to tell the bigger story. Especially, when you're in business for yourself, or in the business of relationships. It's your bio that's read first.
To help you with this, your bio should address the following five questions:
- Who am I?
- How can I help you?
- How did I get here (i.e. know what I know)?
- Why can you trust me?
- What do we share in common?
Your bio is the linchpin for expanding your thought leadership and recognition, especially online. It frames the conversation and sets the tone. It's your job to reveal a bit about yourself and how you see the world. Do this well, and people will eagerly want to engage with you further.
Here's the challenge: who taught you how to write your bio?
Admittedly, most of us never got a lesson in this essential task. You're not alone. Even the most skilled communicators get tongue-tied and twisted when trying to represent themselves in writing. We fear the two extremes: obnoxious self-importance or boring earnestness.
It gets further complicated when you're in the midst of a career or business reinvention. You have to reconcile the different twists and turns of your past into a coherent professional storyline.
The personal branding industry has only muddied the waters. It's easy to feel turned off by the heavy-handed acts of self-promotion that the various gurus out there say you're supposed to do. We've been told to carefully construct a persona that will differentiate and trademark our skills into a unique value proposition.
That's mostly a bunch of buzzword bingo bullshit.
Instead, share more of what you really care about.
And then write your bio in service to your reader, not just ego validation.
Imagine that: A compelling reason to tell your story beyond bragging to the world that you're "kind of a big deal." Embrace the holy-grail of storytelling: tell a story that people can identify with as their own – and the need to persuade, convince, or sell them on anything disappears.
With all this in mind, here's a few key pointers for reinventing your bio as a story:
1. Share a Point of View.
You're a creative. Having something to say is the ultimate proof. What's missing from the larger conversation? Speak to that. Don't be afraid to tell the bigger story. We want to know how you see the world. Show us that you have a unique perspective or fresh vantage point on the things that matter most.
2. Create a Backstory.
Explain the origin for how you came to see the world in this way. Maybe it was something that happened to you as a kid or early in your career. Consider your superhero origins. How did you come into these powers? What set you off on this quest or journey? What's the riddle or mystery you are still trying to solve? When you tell the story of who you were meant to be, it becomes an undeniable story. Natural authority is speaking from the place of what you know and have lived.
3. Incorporate External Validators.
Think frugally here. To paraphrase the artist De La Vega, we spend too much time trying to convince others, instead of believing in ourselves. Nonetheless, if you're doing something new, different, or innovative — you have to anchor it into the familiar. Help people see that your novel ideas are connected to things they recognize and trust. That might be your notable clients, press, publications, or things you've created. Just enough to show people your story is for real.
4. Invite people into relationship.
Now that you've established you've got something to share, remind people you're not so different from them. Vulnerability is the new black. Share some guilty pleasures. Describe what you like to geek out on. Reveal a couple things you obsess about as hobbies or interests. This will make you more approachable and relatable. You're human, too. Help people find the invisible lines of connection.
To revamp your bio, start with these simple storytelling principles and questions above.
In the process, you'll discover a greater potential to shift how you see yourself and how the world sees you. Your story sets the boundaries for everything else that follows.
If you're having trouble being heard, recognized, or understood, it's probably an issue related to your story and identity.
The good news? I want to help, so I created a FREE email course to get you started on your new story.
It's never too late to reinvent your story.
Story on!
Illustration: Oscar Ramos Orozco


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The Food and Agriculture Organization of the United Nations (FAO), the International Food Policy Research Institute (IFPRI) and the CGIAR research program on Policies, Institutions, and Markets (PIM) have launched a new initiative to enhance global cooperation on measuring and reducing food loss and waste.
The G20 agriculture ministers requested FAO and IFPRI to launch this initiative in Istanbul, Turkey in May 2015.
The Technical Platform on the Measurement and Reduction of Food Loss and Waste is an information-sharing and coordination network involving diverse stakeholders, such as international organizations, development banks, non-governmental organizations, and the private sector.
Platform partners will work together to enhance the measurement of food loss and waste, exchange knowledge and information, and share best practices to tackle the global challenges of food loss and waste.
"The G20 Platform will enhance our capacity to accurately measure food loss and waste, both in the G20 countries and in low-income countries," said FAO director-general José Graziano da Silva.
"It will bring new expertise and knowledge for improving metrics. It will also respond to countries' need for knowledge and good practices."
"We must coordinate global efforts to reduce food loss and waste to enhance our ability to sustainably eliminate global hunger and under nutrition," said IFPRI director-general Shenggen Fan.
"This new platform is a critical step in this direction."
Currently, one-third of global food production – enough food to feed two billion people for a year – is lost or wasted annually.
The G20 agriculture ministers noted the significant food loss and waste throughout food value chains as "a global problem of enormous economic, environmental and societal significance".
The platform will:
– Lead efforts to improve the measurement of food loss and waste,
– Build capacity to reduce food loss and waste in G20 countries and in lower-income nations.
This capacity building effort includes 'South-South' knowledge transfers,
– Provide evidence-based advocacy on the scope, causes and costs of food loss and waste,
– Monitor global developments on food loss and waste, and
– Provide multi-agency advisory and technical assistance for work on food loss and waste at the request of governments.
The Platform builds on and complements existing mechanisms, such as the Global Community of Practice on Food Loss Reduction, run jointly out of Rome by FAO, the International Fund for Agricultural Development and the World Food Programme as well as the World Resources Institute's Food Loss and Waste Protocol.
It also expands on the work done by the SAVE FOOD Network, as well as IFPRI's Policies, Institutions and Markets CGIAR research program, an initiative on food loss and waste under a larger portfolio of value chain studies.
IFPRI also measures food loss and waste at all stages – from production and post-production to processing, distribution and consumption – in order to identify the origin and cost of food loss and waste at the local, regional and global level.
Fighting hunger by saving food
About 800 million people in the world suffer from hunger.
Under nutrition remains widespread with some two billion people lacking essential nutrients like iron, zinc and vitamin A.
Juxtaposing this is the rise of overweight and obesity, especially in middle-income countries.
Food is lost when it is spoilt or spilled before reaching the final product or retail stage.
It is wasted when it spoils during retailing or is discarded by consumers.
Most food loss takes place in post-production, harvesting, transportation and storage and is primarily related to inadequate infrastructure in developing countries.
On the other hand, food waste is a problem in the marketing and consumption stages in developed countries.
IFPRI studies have found that infrastructure development is essential to achieve lower post-harvest food loss. Cutting food loss, however, is not a low-cost alternative to achieving food security and nutrition.
Rather, large-scale reduction in post-harvest food loss requires public and private investments and also supports the long-term productivity growth which contributes to food security.
FAO estimates that over 40% of root crops, fruits and vegetables are lost or wasted, along with 35% of fish, 30% of cereals and 20% of oilseeds, meat, and dairy products.
Total food waste represents an economic value of US$1 trillion annually.
FAO studies have also shown that food wastage is responsible for the release of billions of tons of greenhouse gases into the atmosphere, consuming some 250 km3 of water and 1.4 billion hectares of land each year.


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